methyl 4-((4-nitrobenzyl)amino)benzoate | 67490-42-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 4-((4-nitrobenzyl)amino)benzoate
• 英文别名: Methyl 4-[(4-nitrophenyl)methylamino]benzoate
• CAS: 67490-42-0
• 化学式: C₁₅H₁₄N₂O₄
• 分子量: 286.287
• InChiKey: GPRQYNHJNUOGBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-((4-nitrobenzyl)amino)benzoate 在 草酰氯 、 palladium on activated charcoal 、 氢气 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 20.0h， 生成 4-(N-(4-acetamidobenzyl)-2,4-dihydroxybenzamido)benzoic acid
  参考文献：
  名称：

  Identification of Novel Resorcinol Amide Derivatives as Potent and Specific Pyruvate Dehydrogenase Kinase (PDHK) Inhibitors

  摘要：

  Pyruvate dehydrogenase kinases (PDHKs) promote abnormal respiration in cancer cells. Studies with novel resorcinol amide derivatives based on VER-246608 (6) led to the identification of 19n and 19t containing five-membered heteroaromatic rings as unique structural features. These substances possess single-digit nanomolar activities against PDHKs. 19t exhibits higher potencies against PDHK1/2/4 than does 6 and inhibits only PDHKs among 366 kinases. Moreover, 19g, 19l, and 19s were found to be isotype-selective PDHK inhibitors. Molecular dynamics simulations provide a better understanding of how the heteroaromatic rings affect the activities of 19n and 19t on PDHK1/2/3/4. Moreover, 19n possesses a much higher antiproliferative activity against cancer cells than does 6. We demonstrated that the results of PDH assays better correlate with cellular activities than do those of PDHK kinase assays. Furthermore, 19n induces apoptosis of cancer cells via mitochondrial dysfunction, suppresses tumorigenesis, and displays a synergistic effect on satraplatin suppression of cancer cell proliferation.

  DOI：

  10.1021/acs.jmedchem.9b00565
• 作为产物：
  描述：

  对硝基苯甲醛 、 4-氨基苯甲酸甲酯 在 三乙酰氧基硼氢化钠 作用下， 以 乙醚 、 1,2-二氯乙烷 为溶剂， 反应 4.0h， 以23%的产率得到methyl 4-((4-nitrobenzyl)amino)benzoate
  参考文献：
  名称：

  단백질 키나아제 저해제인 벤즈아미드 유도체

  摘要：

  这项发明涉及具有蛋白激酶抑制活性的苯甲酰胺化合物，其药学上可接受的盐，以及包含该化合物作为有效成分的用于预防和治疗由异常细胞生长引起的疾病的药学组合物。这些新型化合物对于主要诱发因素如PDHK蛋白激酶的疾病，如糖尿病、肥胖、癌症等，表现出优越的抑制作用，因此对于由这些蛋白激酶引起的异常细胞生长和代谢引起的疾病的预防和治疗剂是有用的。

  公开号：

  KR20200066463A

文献信息

• 단백질 키나아제 저해제인 벤즈아미드 유도체
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY 한국과학기술연구원(319980077518) BRN ▼209-82-03522

  公开号：KR20200066463A

  公开（公告）日：2020-06-10

  본 발명은 단백질 키나아제 저해활성을 갖는 벤자미드 화합물, 이의 약학적으로 허용 가능한 염, 그리고 이 화합물을 유효성분으로 함유하는 비정상 세포 성장으로 유발되는 질환의 예방 및 치료용 약학적 조성물에 관한 것이다. 본 발명의 신규 화합물은 당뇨, 비만, 암 등의 주요 유발인자인 PDHK 단백질 키나아제에 대하여 우수한 억제 효과를 나타내므로, 이들 단백질 키나아제에 의해 유발되는 PDHK 단백질 키나아제에 의해 유발되는 비정상적인 세포성장 및 대사로 유발되는 질환의 예방 및 치료제로서 유용하다.

  这项发明涉及具有蛋白激酶抑制活性的苯甲酰胺化合物，其药学上可接受的盐，以及包含该化合物作为有效成分的用于预防和治疗由异常细胞生长引起的疾病的药学组合物。这些新型化合物对于主要诱发因素如PDHK蛋白激酶的疾病，如糖尿病、肥胖、癌症等，表现出优越的抑制作用，因此对于由这些蛋白激酶引起的异常细胞生长和代谢引起的疾病的预防和治疗剂是有用的。
• AMINOALKYL-SUBSTITUTED N-THIENYLBENZAMIDE DERIVATIVE
  申请人：ASTELLAS PHARMA INC.

  公开号：US20150031727A1

  公开（公告）日：2015-01-29

  [Problem] To provide a compound that has an intestinal phosphate transporter (NPT-IIb) inhibitory action and is useful as an active ingredient of an agent for treating and/or preventing hyperphosphatemia. [Means for Solution] The present inventors conducted their studies on a compound that has an NPT-IIb inhibitory action and is useful as an active ingredient of an agent for treating and/or preventing hyperphosphatemia. As a result, they created an aminoalkyl-substituted N-thienylbenzamide derivative which has NPT-IIb inhibitory action, thereby completing the present invention. The aminoalkyl-substituted N-thienylbenzamide derivative of the present invention has an NPT-IIb inhibitory action and can be used as an agent for preventing and/or treating hyperphosphatemia.

  【问题】提供一种具有肠道磷酸转运体（NPT-IIb）抑制作用并且可用作治疗和/或预防高磷血症药物的活性成分的化合物。【解决方案】本发明人对一种具有NPT-IIb抑制作用并且可用作治疗和/或预防高磷血症药物的活性成分的化合物进行了研究。结果，他们创造了一种具有NPT-IIb抑制作用的氨基烷基取代的N-噻吩基苯酰胺衍生物，从而完成了本发明。本发明的氨基烷基取代的N-噻吩基苯酰胺衍生物具有NPT-IIb抑制作用，并可用作预防和/或治疗高磷血症的药物。
• AMINOALKYL-SUBSTITUTED N-THIENYL BENZAMIDE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：EP2772490B1

  公开（公告）日：2016-04-06
• US9062032B2
  申请人：——

  公开号：US9062032B2

  公开（公告）日：2015-06-23
• Identification of Novel Resorcinol Amide Derivatives as Potent and Specific Pyruvate Dehydrogenase Kinase (PDHK) Inhibitors
  作者：Hanna Cho、Injae Shin、Kyungseon Cho、Hojong Yoon、Eun Kyung Yoo、Mi-Jin Kim、Sungmi Park、In-Kyu Lee、Nam Doo Kim、Taebo Sim

  DOI：10.1021/acs.jmedchem.9b00565

  日期：2019.9.26

  Pyruvate dehydrogenase kinases (PDHKs) promote abnormal respiration in cancer cells. Studies with novel resorcinol amide derivatives based on VER-246608 (6) led to the identification of 19n and 19t containing five-membered heteroaromatic rings as unique structural features. These substances possess single-digit nanomolar activities against PDHKs. 19t exhibits higher potencies against PDHK1/2/4 than does 6 and inhibits only PDHKs among 366 kinases. Moreover, 19g, 19l, and 19s were found to be isotype-selective PDHK inhibitors. Molecular dynamics simulations provide a better understanding of how the heteroaromatic rings affect the activities of 19n and 19t on PDHK1/2/3/4. Moreover, 19n possesses a much higher antiproliferative activity against cancer cells than does 6. We demonstrated that the results of PDH assays better correlate with cellular activities than do those of PDHK kinase assays. Furthermore, 19n induces apoptosis of cancer cells via mitochondrial dysfunction, suppresses tumorigenesis, and displays a synergistic effect on satraplatin suppression of cancer cell proliferation.